Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers
Silencing of the MLH1 gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of MLH1 promoters in endometrial cancers and in the normal endometrium is largely unknown...
Gespeichert in:
| Veröffentlicht in: | Oncogene 2003-04, Vol.22 (15), p.2352-2360 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2360 |
|---|---|
| container_issue | 15 |
| container_start_page | 2352 |
| container_title | Oncogene |
| container_volume | 22 |
| creator | Kanaya, Taro Kyo, Satoru Maida, Yoshiko Yatabe, Noriyuki Tanaka, Masaaki Nakamura, Mitsuhiro Inoue, Masaki |
| description | Silencing of the
MLH1
gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of
MLH1
promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study investigates the region 700 bp upstream of
MLH1
covering 48 CpG sites using bisulfite sequencing. Methylation status was classified as full (over 80% of CpGs are methylated), partial (10–80%) or nonmethylation (less than 10%). Of 56 endometrioid endometrial cancers, 16 (29%) were fully methylated, 14 (25%) were partially methylated and 26 (46%) were Q1not methylated. Analyses of
MLH1
by immunohistochemical means and of MSI revealed that the Q2degree, rather than region-specific methylation of CpG islands is critical for decreased MLH1 expression and the MSI phenotype. Among 12 patients with methylated cancers, five (42%) patients contained methylated promoters in their normal endometria with profiles similar to those of cancer lesions, and these were associated with the MSI phenotype. In contrast, only one of 31 (3%) normal endometria from patients without endometrial malignancies harbored methylated promoters. These findings suggest that hypermethylation of the
MLH1
promoter is frequent in the histologically normal endometrium adjacent to cancers, supporting the notion that hypermethylation of mismatch repair genes is the initial step that triggers various genetic events in endometrial carcinogenesis. |
| doi_str_mv | 10.1038/sj.onc.1206365 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_18750391</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A189218834</galeid><sourcerecordid>A189218834</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-787623275992ac50c279cbeb5f50c0cd3dbb9c2b3b0490845786de096b607f253</originalsourceid><addsrcrecordid>eNp1kc-L1DAUx4Mo7uzq1aMUZb119iVpfh2XxXWFES96Dmma7mRokzFpkfnvzTCFgrDkkJD3eS_fb74IfcCwxUDlXT5sY7BbTIBTzl6hDW4ErxlTzWu0AcWgVoSSK3Sd8wEAhALyFl1hIgC4gA1yj8n9mV2Yqv3p6NLopv1pMJOPoYp99WP3hKtjimOcXKp8qEJMoxkqF7pY0OTn8YwdS0MZkau_ftqvxQJaE6xL-R1605shu_fLfoN-P3799fBU735--_5wv6stI3yqhRS8qBVMKWIsA0uEsq1rWV_OYDvata2ypKUtNApkw4TknQPFWw6iJ4zeoC-XuUVzcZUnPfps3TCY4OKcNZaCAVW4gJ__Aw9xTqFo04Q3mBLJJSnUpxcpIiglWPECbS_Qsxmc9qGPUzK2rM6N3sbgel_u77FUBEtJm7XBpphzcr0-Jj-adNIY9DlUnQ-6hKqXUEvDx0XG3I6uW_ElxQLcLoDJ1gx9Kr_u88o1AjPcnF3fXbhcSuHZpdXPC0__A1ItuZk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>227332196</pqid></control><display><type>article</type><title>Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers</title><source>MEDLINE</source><source>Nature</source><source>SpringerNature Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Kanaya, Taro ; Kyo, Satoru ; Maida, Yoshiko ; Yatabe, Noriyuki ; Tanaka, Masaaki ; Nakamura, Mitsuhiro ; Inoue, Masaki</creator><creatorcontrib>Kanaya, Taro ; Kyo, Satoru ; Maida, Yoshiko ; Yatabe, Noriyuki ; Tanaka, Masaaki ; Nakamura, Mitsuhiro ; Inoue, Masaki</creatorcontrib><description>Silencing of the
MLH1
gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of
MLH1
promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study investigates the region 700 bp upstream of
MLH1
covering 48 CpG sites using bisulfite sequencing. Methylation status was classified as full (over 80% of CpGs are methylated), partial (10–80%) or nonmethylation (less than 10%). Of 56 endometrioid endometrial cancers, 16 (29%) were fully methylated, 14 (25%) were partially methylated and 26 (46%) were Q1not methylated. Analyses of
MLH1
by immunohistochemical means and of MSI revealed that the Q2degree, rather than region-specific methylation of CpG islands is critical for decreased MLH1 expression and the MSI phenotype. Among 12 patients with methylated cancers, five (42%) patients contained methylated promoters in their normal endometria with profiles similar to those of cancer lesions, and these were associated with the MSI phenotype. In contrast, only one of 31 (3%) normal endometria from patients without endometrial malignancies harbored methylated promoters. These findings suggest that hypermethylation of the
MLH1
promoter is frequent in the histologically normal endometrium adjacent to cancers, supporting the notion that hypermethylation of mismatch repair genes is the initial step that triggers various genetic events in endometrial carcinogenesis.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1206365</identifier><identifier>PMID: 12700670</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adaptor Proteins, Signal Transducing ; Apoptosis ; Base Pair Mismatch ; Biological and medical sciences ; Bisulfite ; Carcinogenesis ; Carcinoma, Endometrioid - chemistry ; Carcinoma, Endometrioid - genetics ; Carrier Proteins ; Cell Biology ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cell Transformation, Neoplastic - genetics ; CpG Islands ; Dinucleotide Repeats ; DNA Methylation ; DNA Repair - genetics ; DNA, Neoplasm - chemistry ; DNA, Neoplasm - genetics ; Endometrial cancer ; Endometrial Neoplasms - chemistry ; Endometrial Neoplasms - genetics ; Endometrium ; Endometrium - chemistry ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Neoplastic ; Genes ; Genotype & phenotype ; Human Genetics ; Humans ; Internal Medicine ; Medicine ; Medicine & Public Health ; Microsatellite instability ; Microsatellite Repeats ; Mismatch repair ; MLH1 protein ; Molecular and cellular biology ; Mutation ; MutL Protein Homolog 1 ; Neoplasm Proteins - genetics ; Nuclear Proteins ; oncogenomics ; Oncology ; Phenotype ; Phenotypes ; Promoter Regions, Genetic ; Promoters ; Tumors ; Yeast</subject><ispartof>Oncogene, 2003-04, Vol.22 (15), p.2352-2360</ispartof><rights>Springer Nature Limited 2003</rights><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 17, 2003</rights><rights>Nature Publishing Group 2003.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-787623275992ac50c279cbeb5f50c0cd3dbb9c2b3b0490845786de096b607f253</citedby><cites>FETCH-LOGICAL-c526t-787623275992ac50c279cbeb5f50c0cd3dbb9c2b3b0490845786de096b607f253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1206365$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1206365$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14715141$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12700670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kanaya, Taro</creatorcontrib><creatorcontrib>Kyo, Satoru</creatorcontrib><creatorcontrib>Maida, Yoshiko</creatorcontrib><creatorcontrib>Yatabe, Noriyuki</creatorcontrib><creatorcontrib>Tanaka, Masaaki</creatorcontrib><creatorcontrib>Nakamura, Mitsuhiro</creatorcontrib><creatorcontrib>Inoue, Masaki</creatorcontrib><title>Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Silencing of the
MLH1
gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of
MLH1
promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study investigates the region 700 bp upstream of
MLH1
covering 48 CpG sites using bisulfite sequencing. Methylation status was classified as full (over 80% of CpGs are methylated), partial (10–80%) or nonmethylation (less than 10%). Of 56 endometrioid endometrial cancers, 16 (29%) were fully methylated, 14 (25%) were partially methylated and 26 (46%) were Q1not methylated. Analyses of
MLH1
by immunohistochemical means and of MSI revealed that the Q2degree, rather than region-specific methylation of CpG islands is critical for decreased MLH1 expression and the MSI phenotype. Among 12 patients with methylated cancers, five (42%) patients contained methylated promoters in their normal endometria with profiles similar to those of cancer lesions, and these were associated with the MSI phenotype. In contrast, only one of 31 (3%) normal endometria from patients without endometrial malignancies harbored methylated promoters. These findings suggest that hypermethylation of the
MLH1
promoter is frequent in the histologically normal endometrium adjacent to cancers, supporting the notion that hypermethylation of mismatch repair genes is the initial step that triggers various genetic events in endometrial carcinogenesis.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Apoptosis</subject><subject>Base Pair Mismatch</subject><subject>Biological and medical sciences</subject><subject>Bisulfite</subject><subject>Carcinogenesis</subject><subject>Carcinoma, Endometrioid - chemistry</subject><subject>Carcinoma, Endometrioid - genetics</subject><subject>Carrier Proteins</subject><subject>Cell Biology</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>CpG Islands</subject><subject>Dinucleotide Repeats</subject><subject>DNA Methylation</subject><subject>DNA Repair - genetics</subject><subject>DNA, Neoplasm - chemistry</subject><subject>DNA, Neoplasm - genetics</subject><subject>Endometrial cancer</subject><subject>Endometrial Neoplasms - chemistry</subject><subject>Endometrial Neoplasms - genetics</subject><subject>Endometrium</subject><subject>Endometrium - chemistry</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genotype & phenotype</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Microsatellite instability</subject><subject>Microsatellite Repeats</subject><subject>Mismatch repair</subject><subject>MLH1 protein</subject><subject>Molecular and cellular biology</subject><subject>Mutation</subject><subject>MutL Protein Homolog 1</subject><subject>Neoplasm Proteins - genetics</subject><subject>Nuclear Proteins</subject><subject>oncogenomics</subject><subject>Oncology</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Promoter Regions, Genetic</subject><subject>Promoters</subject><subject>Tumors</subject><subject>Yeast</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kc-L1DAUx4Mo7uzq1aMUZb119iVpfh2XxXWFES96Dmma7mRokzFpkfnvzTCFgrDkkJD3eS_fb74IfcCwxUDlXT5sY7BbTIBTzl6hDW4ErxlTzWu0AcWgVoSSK3Sd8wEAhALyFl1hIgC4gA1yj8n9mV2Yqv3p6NLopv1pMJOPoYp99WP3hKtjimOcXKp8qEJMoxkqF7pY0OTn8YwdS0MZkau_ftqvxQJaE6xL-R1605shu_fLfoN-P3799fBU735--_5wv6stI3yqhRS8qBVMKWIsA0uEsq1rWV_OYDvata2ypKUtNApkw4TknQPFWw6iJ4zeoC-XuUVzcZUnPfps3TCY4OKcNZaCAVW4gJ__Aw9xTqFo04Q3mBLJJSnUpxcpIiglWPECbS_Qsxmc9qGPUzK2rM6N3sbgel_u77FUBEtJm7XBpphzcr0-Jj-adNIY9DlUnQ-6hKqXUEvDx0XG3I6uW_ElxQLcLoDJ1gx9Kr_u88o1AjPcnF3fXbhcSuHZpdXPC0__A1ItuZk</recordid><startdate>20030417</startdate><enddate>20030417</enddate><creator>Kanaya, Taro</creator><creator>Kyo, Satoru</creator><creator>Maida, Yoshiko</creator><creator>Yatabe, Noriyuki</creator><creator>Tanaka, Masaaki</creator><creator>Nakamura, Mitsuhiro</creator><creator>Inoue, Masaki</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20030417</creationdate><title>Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers</title><author>Kanaya, Taro ; Kyo, Satoru ; Maida, Yoshiko ; Yatabe, Noriyuki ; Tanaka, Masaaki ; Nakamura, Mitsuhiro ; Inoue, Masaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-787623275992ac50c279cbeb5f50c0cd3dbb9c2b3b0490845786de096b607f253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Apoptosis</topic><topic>Base Pair Mismatch</topic><topic>Biological and medical sciences</topic><topic>Bisulfite</topic><topic>Carcinogenesis</topic><topic>Carcinoma, Endometrioid - chemistry</topic><topic>Carcinoma, Endometrioid - genetics</topic><topic>Carrier Proteins</topic><topic>Cell Biology</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>CpG Islands</topic><topic>Dinucleotide Repeats</topic><topic>DNA Methylation</topic><topic>DNA Repair - genetics</topic><topic>DNA, Neoplasm - chemistry</topic><topic>DNA, Neoplasm - genetics</topic><topic>Endometrial cancer</topic><topic>Endometrial Neoplasms - chemistry</topic><topic>Endometrial Neoplasms - genetics</topic><topic>Endometrium</topic><topic>Endometrium - chemistry</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genotype & phenotype</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Microsatellite instability</topic><topic>Microsatellite Repeats</topic><topic>Mismatch repair</topic><topic>MLH1 protein</topic><topic>Molecular and cellular biology</topic><topic>Mutation</topic><topic>MutL Protein Homolog 1</topic><topic>Neoplasm Proteins - genetics</topic><topic>Nuclear Proteins</topic><topic>oncogenomics</topic><topic>Oncology</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Promoter Regions, Genetic</topic><topic>Promoters</topic><topic>Tumors</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kanaya, Taro</creatorcontrib><creatorcontrib>Kyo, Satoru</creatorcontrib><creatorcontrib>Maida, Yoshiko</creatorcontrib><creatorcontrib>Yatabe, Noriyuki</creatorcontrib><creatorcontrib>Tanaka, Masaaki</creatorcontrib><creatorcontrib>Nakamura, Mitsuhiro</creatorcontrib><creatorcontrib>Inoue, Masaki</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kanaya, Taro</au><au>Kyo, Satoru</au><au>Maida, Yoshiko</au><au>Yatabe, Noriyuki</au><au>Tanaka, Masaaki</au><au>Nakamura, Mitsuhiro</au><au>Inoue, Masaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2003-04-17</date><risdate>2003</risdate><volume>22</volume><issue>15</issue><spage>2352</spage><epage>2360</epage><pages>2352-2360</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Silencing of the
MLH1
gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of
MLH1
promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study investigates the region 700 bp upstream of
MLH1
covering 48 CpG sites using bisulfite sequencing. Methylation status was classified as full (over 80% of CpGs are methylated), partial (10–80%) or nonmethylation (less than 10%). Of 56 endometrioid endometrial cancers, 16 (29%) were fully methylated, 14 (25%) were partially methylated and 26 (46%) were Q1not methylated. Analyses of
MLH1
by immunohistochemical means and of MSI revealed that the Q2degree, rather than region-specific methylation of CpG islands is critical for decreased MLH1 expression and the MSI phenotype. Among 12 patients with methylated cancers, five (42%) patients contained methylated promoters in their normal endometria with profiles similar to those of cancer lesions, and these were associated with the MSI phenotype. In contrast, only one of 31 (3%) normal endometria from patients without endometrial malignancies harbored methylated promoters. These findings suggest that hypermethylation of the
MLH1
promoter is frequent in the histologically normal endometrium adjacent to cancers, supporting the notion that hypermethylation of mismatch repair genes is the initial step that triggers various genetic events in endometrial carcinogenesis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>12700670</pmid><doi>10.1038/sj.onc.1206365</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2003-04, Vol.22 (15), p.2352-2360 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_18750391 |
| source | MEDLINE; Nature; SpringerNature Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Adaptor Proteins, Signal Transducing Apoptosis Base Pair Mismatch Biological and medical sciences Bisulfite Carcinogenesis Carcinoma, Endometrioid - chemistry Carcinoma, Endometrioid - genetics Carrier Proteins Cell Biology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cell Transformation, Neoplastic - genetics CpG Islands Dinucleotide Repeats DNA Methylation DNA Repair - genetics DNA, Neoplasm - chemistry DNA, Neoplasm - genetics Endometrial cancer Endometrial Neoplasms - chemistry Endometrial Neoplasms - genetics Endometrium Endometrium - chemistry Female Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Neoplastic Genes Genotype & phenotype Human Genetics Humans Internal Medicine Medicine Medicine & Public Health Microsatellite instability Microsatellite Repeats Mismatch repair MLH1 protein Molecular and cellular biology Mutation MutL Protein Homolog 1 Neoplasm Proteins - genetics Nuclear Proteins oncogenomics Oncology Phenotype Phenotypes Promoter Regions, Genetic Promoters Tumors Yeast |
| title | Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T17%3A09%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Frequent%20hypermethylation%20of%20MLH1%20promoter%20in%20normal%20endometrium%20of%20patients%20with%20endometrial%20cancers&rft.jtitle=Oncogene&rft.au=Kanaya,%20Taro&rft.date=2003-04-17&rft.volume=22&rft.issue=15&rft.spage=2352&rft.epage=2360&rft.pages=2352-2360&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/sj.onc.1206365&rft_dat=%3Cgale_proqu%3EA189218834%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=227332196&rft_id=info:pmid/12700670&rft_galeid=A189218834&rfr_iscdi=true |